4.4 Article

Antitumor effects of cadmium against diethylnitrosamine-induced liver tumors in mice

Journal

ONCOLOGY LETTERS
Volume 23, Issue 1, Pages -

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2021.13151

Keywords

cadmium; diethylnitrosamine; carbon tetrachloride; liver tumors; ultrasound; metallothionein

Categories

Funding

  1. Guizhou Provincial Science and Technology Program [QKH(2019)1346]
  2. Science and Technology Talent Support Project of the Educational Department of Guizhou Province [KY(2018)055]
  3. Innovation Talent Team of Zunyi [ZSKRC(2019)1]
  4. Innovation Talent Team of Guizhou Science and Technology Department [QKHPTRC(2020)5007]
  5. Science and Technology Plan of Zunyi [ZSKRCPT(2020)7]

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The study found that cadmium has inhibitory effects on chemically induced liver tumors, which may be related to the deficiency of metallothionein in tumors and the induction of TNF-α in tumor cells.
Cadmium (Cd) has been reported to exhibit antitumor effects against chemically induced liver tumors. However, the antitumor effects of Cd are not completely understood. Metallotherapy, the use of a toxic metal to attack liver tumors, could be a viable strategy. In the present study, 8-week old, male, C57BL/6 mice were administered injections of diethylnitrosamine (DEN) (90 mg/kg, and then 50 mg/kg 2 weeks later), followed by liver tumor promotion with carbon tetrachloride. Cadmium chloride was administered in the drinking water (1000 ppm) from 21-40 weeks after DEN initiation. Body weights were recorded and liver tumor formation was monitored via ultrasound. At the end of experiments, livers were removed, weighed, and the tumor incidence, tumor numbers and tumor size scores were recorded. Liver histology and metallothionein (MT) immunostaining were performed. After DEN injection, animal body weight decreased, and then slowly recovered with time. Cd treatment did not affect animal body weight gain. Ultrasound analysis detected liver tumors 35 weeks after DEN injection, and the mice were necropsied at 40 weeks. Liver/body weight ratios increased in the DEN and DEN + Cd groups. Cd treatment decreased the tumor incidence (71 vs. 17%), tumor numbers (15 vs. 2) and tumor scores (22 vs. 3) when compared with the DEN only group. Histopathology showed hepatocyte degeneration in all groups, and immunohistochemistry showed MT-deficiency in the liver tumors, while MT staining was intensified in the surrounding tissues. Reverse transcription-quantitative PCR showed increases in alpha-fetoprotein level in DEN-treated livers, and increases in MT-2 and tumor necrosis factor alpha (TNF alpha) levels in Cd-treated livers. Thus, it was concluded that Cd is effective in the suppression of DEN-induced liver tumors, and that the mechanisms may be related to MT-deficiency in tumors and the induction of TNF alpha to kill tumor cells.

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